Ординатура / Офтальмология / Английские материалы / Keratoconus Sugery and Cross-Linking_Pinelli, Leccisotti_2008

Penetrating Keratoplasty

FIGURES 13-16A AND B: (A) At the end of the operation, the viscoelastic material is exchanged for a balanced salt solution before tying the last suture. (B) Shown is a set of 16-interrupted sutures after the suture knots are buried.

FIGURES 13-17A AND B: Shown is a single continuous running suture (A) and a double continuous running suture (B).

FIGURE 13-18: Schematic suture technique for a single continuous running suture. Some surgeons believe that an anti-torque running suture is helpful in reducing astigmatism, whereas others have not observed any significant effects with such a suture.

Antitorque pattern of single running suture. On the left, the overlying radial sutures (full line) would result in a minimal suture torque and a reduced risk of induced astigmatism. Intrastromal suture bites (dotted line) are antitorque.

Torque pattern of single running suture. On the right, the intrastromal suture is radial (dotted line), and the overlying torquing suture bites (full line) could rotate the graft in the arrow direction and induce astigmatism.

the graft rather than in the recipient side to minimize vascularization. The total number of interrupted sutures and passages of the running suture is usually between 16 and 24.

Readjustment of Sutures to Minimize Astigmatism

When a running suture is carried out, it is necessary to harmoniously distribute its tension before burying the knot. The tension of the sutures may be checked at the end of the operation after 139 replacing the viscoelastic material in the anterior chamber with balanced salt solution (Figure 13-16).

Keratoconus Surgery and Cross-linking

FIGURE 13-19: Alignment of the graft and host epithelial surfaces during suturing is critical. Differences between suture depths in the graft versus the host may cause sectorial overrides of the graft over the host, resulting in a giant postoperative astigmatism.

FIGURES 13-20A AND B: (A) At the end of the operation, the reflex of the circular rings of the keratoscope enables the observation of the suture tensions. The reflex must find circular mires that show homogenous tensions of the sutures.

(B) The wound is tested for water tightness. This is done after drying the surface with a cellulose sponge pressing at the limbus and by observing the wound for leakage of aqueous humor.

A disposable keratoscope may be used to this effect (Figure 13-20A). A suture adjustment may be done until regular circular mires are obtained. Interrupted sutures that are too tight along the shorter diameter of the oval may be replaced by sutures that have optimal tension to help achieve a circular shape of the mires. The tension of the running suture can be modified by rotation.

Administering Medications

At the end of the operation, the wound is tested to ensure it is watertight (Figure 13-20B), and 140 topical antibiotic and corticosteroids eyedrops are applied.

Penetrating Keratoplasty

POSTOPERATIVE MANAGEMENT

Postoperative treatment usually consists of corticosteroids eyedrops associated with antibiotic eyedrops. The corticosteroids used are Dexamethasone, Fluorometholone, Rimexolone and Hydrocortisone. The treatment can be commenced with 3 to 4 daily instillations and finished with an instillation every two days, and the corticosteroids eyedrops are usually stopped after a period of 12 to 24 months. Topical corticosteroids can be stopped when all of the sutures are removed or even earlier if they aren’t going to be removed.

Postoperative management of the sutures enables guided healing and reduces post-graft astigmatism. The choice of sutures to be removed or the areas of a running suture to be loosened can be guided by a corneal topography. Selective ablation of interrupted sutures and adjustment of the tension of a running suture (Figure 13-21) give similar results in terms of reduction of postoperative astigmatism.20, 21 Because of the risk of sutures breaking during the adjustment procedure, suture adjustment should not be attempted unless facilities are available to make the repair. The choice to leave in place the sutures long term or to remove all of the sutures is sometimes difficult. Usually, it is desirable to leave most of the sutures in place for at least 12 to 18 months. An earlier ablation of all of the sutures may lead to a gap in the wound and even to a wound dehiscence. Suture removal, even years out from a PK, should not be viewed as risk free. Prior to and following suture removal or manipulation, all patients should be given corticosteroids prophylaxis to avoid possible corneal allograft rejection.

Successful follow-up of grafted patients is a major factor in the prognosis of the graft. Postoperative complications are often reversible and correctible as long as they are diagnosed and treated early.

FIGURE 13-21: Rotation of a continuous running suture to correct against the rule astigmatism of 5 diopters. Rotation of the sutures is done from the flat (2) to the steep meridian (1) simultaneously flattening the steep meridian and steepening the flat meridian.

Results

The survival rate of the graft in the medium term follow-up (2 to 5 years) is around 95% in keratoconus.22-28 Sharif and Casey,23 using data from a case series of 100 eyes with an average followup of 6.1 years, reported a 93% survival rate. Lim, et al26 using data from 93 eyes followed for an average 46.5 months, reported a failure rate of only 1.02%. With a longer follow-up of 13.8 years (range from 0.5 to 30.4 years) of 112 eyes, Pramanik, et al28 reported a 93.7% survival rate. The two

essential causes of graft failure after PK for keratoconus are allogenic graft rejection and non-immune 141 secondary endothelial decompensation of the graft. The survival rate of a PK after keratoconus is

Keratoconus Surgery and Cross-linking

one of the highest. Thompson, et al27 reported on a series of 3992 PK with an average follow-up of 43

± 34 months. The survival rate of the grafts after keratoconus (n=449 eyes) was 98%. By comparison, the survival rate of the grafts after pseudophakic bullous keratopathy (n=315) was 88%, 81% after aphakic bullous keratopathy (n=105), 96% after Fuchs dystrophy (n=908), 88% for herpetic keratitis (n=77), and 68% after a second graft (n=352).

The visual results are good in the majority of cases, with best corrected visual acuity (BCVA) greater than or equal to 0.5 (20/40) in 70 to 91% of patients.26, 29-35 Olson et al29 reported that 87% of eyes had a BCVA of 0.8 (20/25). Visual rehabilitation is often slow. The majority of patients require optical correction after PK. In the study by Olson, et al the three main causes of postoperative corrected visual acuity limited to less than 0.8 were cataract, graft rejection and superficial punctate keratitis (found in 20% of cases at 6 months). Lim, et al26 reported that visual acuity greater than 0.5 (20/40) was observed 87% of cases at the end of the follow-up (0.63 on average). After PK, 67% of eyes were corrected by glasses, 28% by contact lenses and 7% did not wear any corrective devices.

Patients are often shortsighted following PK for keratoconus. Brierly, et al30 reported a corrected visual acuity greater than 0.5 in 84% of cases at 18 months (0.76 on average). The uncorrected visual acuity was 0.28 at 18 months. The average spherical equivalent at one year was -4.13 ± 4.41 diopters

(D) with an average cylinder of 2.52 ± 2.45 D.

PK improves contrast sensitivity and the stereoscopic visual acuity of keratoconus.36, 37

Complications and Their Management

INTRAOPERATIVE COMPLICATIONS

The major intraoperative complication of PK is expulsive choroidal hemorrhage during the open-sky phase of keratoplasty. Its incidence varies from 0.47% to 3.3%.38, 39 Sometimes it presents as a postoperative choroidal detachment or choroidal hemorrhage. With open-sky expulsive hemorrhages, an immediate posterior sclerotomy via a stab incision through the conjunctiva and sclera must be performed. Because number 9-0 or 10-0 nylon may not be sufficient to secure the wound, number 8- 0 nylon or even 6-0 or 7-0 silk sutures should be used.

Other, less severe, traumatic complications may appear, such as injury to the lens and iris particularly during trephination in thinned corneas. Iris-lens damage should be repaired. Iris damage or iridodialysis are repaired with a 10-0 polypropylene suture. If the anterior lens capsule has been opened, an extracapsular cataract extraction should be performed with placement of a posterior chamber intraocular lens.

POSTOPERATIVE COMPLICATIONS

Corneal Allograft Rejection

Corneal allograft rejection is the main cause of graft failure after PKs for keratoconus. A higher risk of rejection is associated with a young recipient age, corneal neovascularization of the recipient (Figure 13-22), a large-diameter corneal graft, and prior graft failure, particularly due to rejection. The rejection rate of corneal grafts varies from 20 to 35% in the literature.29, 35, 40,41 Olson, et al29 reported a corneal allograft rejection in 31% of cases, and in 36 of such cases, 7 had recurrences of rejection. The majority of graft rejections were observed between 1 and 2 years after surgery. The

142 types of rejections were as follows: 12 out of 36 were epithelial rejections, 15 out of 36 were endothelial rejections (Figure 13-23) and 9 out of 36 were mixed rejections. In contrast, the graft failure rate

Penetrating Keratoplasty

FIGURE 13-22: Corneal vascularization may be favored by an interrupted or continuous suture. Vascularized suture increases the risk of graft rejection.

FIGURE 13-23: Allogenic endothelial corneal graft rejection with a Khodadoust rejection line and diffuse keratic precipitates.

Keratoconus Surgery and Cross-linking

Corneal Graft Astigmatism

Astigmatism is the main source of limitation in visual acuity after PK in patients with a clear graft. Several factors contribute to astigmatism after PK: trephination of the graft and of the recipient cornea, astigmatism of the recipient cornea and of the graft, a gap between the recipient cornea and the graft (Figure 13-19), tension of the sutures, the quality of the wound healing and the experience of the surgeon. Olson et al29 reported an improved astigmatism with postoperative follow-up: 6.14 ± 4.12 D before surgery, 4.04 ± 2.45 D at 1 month, 2.86 ± 2.14 D at 1 year and 2.76 ± 1.99 D at 2 years (after surgical management of the astigmatism in some cases). If the suture-related astigmatism can be partially corrected by postoperative management of the sutures (Figure 13-21), the other causes of astigmatism can only be corrected surgically. In practice, the most difficult problem is that of giant astigmatism (> 5 D) in a patient who has had all of the sutures removed. When this type of astigmatism limits the corrected visual acuity and correction with glasses or contact lenses cannot be tolerated, surgery for the astigmatism must be considered. This must only be done after some time (after around 6 months minimum) from the ablation of the last suture and in a patient whose astigmatism is stable on at least two examinations with an interval of several months.

The techniques most used are relaxing incisions including arcuate, transverse, and trapezoidal keratotomies made with a diamond knife (Figure 13-24). The complications of astigmatic keratotomies are perforation, infection and rejection. Prophylactic anti-rejection therapy, using topical

FIGURES 13-24A TO F: Astigmatic keratotomy. A) The reflex of the keratoscope mires shows an inverse astigmatism. The steepest meridian is on the horizontal axis (along the shorter diameter of the oval). (B) Location of the 180° meridian on which the incisions are tobemade. (C)Micrometerdiamond blade is set according to the preoperative pachymetry 1 mm or so inside the periphery of the graft.

(D) The incisions must be deep (80 to 90% of the corneal thickness), perpendicular to the graft surface, and located either inside the grafthost junction or in the wound itself.

(E) The incisions are washed with BSS. (F) Intraoperative astigmatism reassessment enables a flattening of the horizontal meridian to be observed. The reflex mires of the keratoscope are more circular. The persistence of an inverse astigmatism can require other incisions concentric to the first one during the same session or remotely after

144 having assessed the full effect of the initial incisions.

Penetrating Keratoplasty

FIGURES 13-25A TO C: Wedge excision. (A) Corneal graft astigmatism is very asymmetrical in this case. An arcuate wedge of graft tissue is excised from the donor margin in the flat axis (B) causing steepening of the flat axis. (C) The wound is resutured. Excision of a 1 mm wedge of tissue can correct 8 dioptres of astigmatism.

FIGURE 13-26: Topography-guided laser in situ keratomileusis (Topolink) for the correction of a corneal graft irregular astigmatism. The preoperative topographic map (B) shows marked asymmetry of the astigmatism. The topolink computer calculates a customized ablation profile (C). The postoperative map (A) shows significantly improved astigmatism symmetry within the 3 mm central zone. The differential map (A-B) shows the asymmetric ablation pattern, customized to this individual eye. Visual acuity improved from 0.3 with –9 –5x25 to 0.6 with –7 –2x30.

corticosteroids, is mandatory for at least a month following relaxing incisions. Other techniques (such as compression sutures alone or in association with relaxing incisions and wedge resection) are less frequently used. Wedge resections (Figure 13-25) are aimed at major astigmatisms, often asymmetrical, with often unpredictable results.

The success of LASIK in reducing postkeratoplasty astigmatism has dramatically altered the postoperative management of keratoplasty patients. Topography-guided laser in situ keratomileusis (Topolink) (Figure 13-26) gives encouraging results in post-graft irregular astigmatisms.

Finally, the use of phakic toric intraocular lenses may be a helpful alternative in treating 145 postkeratoplasty astigmatism and ametropia.

Keratoconus Surgery and Cross-linking

Side Effects of Topical Corticosteroids

Glaucoma and cataract may occur.

Intraocular pressure elevation is the second leading cause of graft failure after PK. In patients with keratoconus, it is then often secondary to corticosteroids. Sustained elevation of intraocular pressure not only damages the optic nerve head, but it also has a deleterious effect on the corneal endothelium. Correction of elevated intraocular pressure refers to a reduction in corticosteroids eyedrops (e.g. replacement of Dexamethasone with Fluorometholone), the use of topical or systemic antiglaucoma medications, and even traditional filtering surgery on rare occasions (when either the optic nerve or the graft is threatened by persistent elevation of intraocular pressure).

Cataract can be extracted through a separate incision after the wound is totally healed. The endothelium must be protected by a good viscoelastic because of the risk of endothelial decompensation. Cataract extraction in a young subject results in a constant loss of accommodation.

Other Complications

Shallow anterior chamber and wound leak: Lack of water tightness of the wound in the early postoperative period can be due to a full thickness suture or an insufficient number of sutures. Additional sutures may be applied in the operating room under topical anesthesia.

Epithelial defects: Epithelial defects are the source of visual loss, infection, rejection, stromal melting, perforations, and even graft failure. Survival of a corneal graft is critically dependent on an intact epithelial barrier. The quality of the postoperative epithelial wound healing necessitates frequent use of lubricants, preferably preservative-free, to promote epithelial growth, as well as the use of a bandage soft contact lens with high oxygen permeability in certain occasions.

Urrets-Zavalia syndrome: The first description of Urrets-Zavalia syndrome or fixed dilated pupil was made by Urrets-Zavalia after a corneal graft for keratoconus.42 However, this syndrome is not specific to PK in keratoconus, and it was reported following lamellar grafts and in other indications. The mechanism is poorly understood, but it may involve iris ischemia. The role of mydriatics has been brought up as well as that of early and transitory acute postoperative raised intraocular pressure. Although rare, this complication prompts the use of mydriatics to be limited unless it is absolutely necessary. A careful ablation of viscoelastic at the end of the operation seems just as suitable, in our clinical experience.

Infections after PK: Postoperative endophthalmitis is a rare but sight-threatening complication of PK. Its incidence is around 0.5%.43 Often, the infectious agents come from the conjunctival and palpebral flora of the patient. The clinical signs, diagnosis and treatment of postoperative endophthalmitis after PK are the same as those for endophthalmitis after cataract surgery.

Bacterial and fungal keratitis are complications that usually involve the graft or the wound. The incidence of microbial keratitis ranges from 1 to 12% in patients operated for PK. Microbial keratitis may be more frequent with topical steroids, persistent epithelial defect and suture related problems. It presents in the form of a stromal abscess with a high risk of graft melting. A particular form is an infectious crystalline keratopathy which takes the appearance of crystalline branching opacities (Figure 13-27). The most common organism causing crystalline keratopathy is Streptococcus viridans. The identification of the etiology must be done with corneal scrapings for smear and culture in appropriate media, as fungal species have also been implicated. Treatment for bacterial and fungal keratitis is

146 based on intensive regimen of broad-spectrum, fortified antibiotic eyedrops often with systemic

Penetrating Keratoplasty

FIGURES 13-27A AND B: (A) Streptococcus viridans infectious crystalline keratopathy. (B) Note the crystalline opacities in the anterior and mid stroma.

drugs. A therapeutic graft is sometimes necessary. Fungal keratitis may necessitate interruption of the corticosteroids in the acute phase. The corticosteroids can be substituted with topical 2% Cyclosporin, which, in addition to its anti-rejection action, possesses an anti-fungal action.44

Recurrence of herpes simplex keratitis in a graft is not uncommon. Herpes simplex keratitis may also be observed in a patient who has never had herpes simplex keratitis. It has the distinctive feature of inciting graft rejection. Therefore, the treatment must include topical antiviral agents (administered topically and generally), and corticosteroids in the case of stromal keratitis.

In all cases, the prognosis of the initial graft is affected by these postoperative infections that confer an increased risk of graft failure.

Traumas on the grafted eye: Traumas on the grafted eye may have disastrous consequences and may even lead to the loss of the eye. Even after a long period of time from the trauma, a risk of wound dehiscence may persist.

Non-immunologic endothelial decompensation of the graft: The endothelial decompensation of the graft is another cause of graft failure of PK with progressive endothelial cell loss. Ing, et al45 reported the outcomes of a series of 394 eyes with PK, 119 of which were followed for 10 years. Endothelial cell loss, from all causes, was 4.2% per year over a period of 5 to 10 years after the graft. This was 7 times greater than the average normal loss estimated at 0.6% per year. Out of 48 eyes grafted for keratoconus (40.3%) and followed up after 10 years, the endothelial cell loss was 73 ± 9% in 10 years compared with preoperative values. It was 23 ± 30% between 5 and 10 years after the graft. This progressive endothelial cell loss is the cause of the emptying of the peripheral endothelial reservoir that greatly reduces the chances of survival of the graft and any subsequent grafts. Thus, this must be taken into account in the decision to operate in young subjects.

Vitreoretinal complications: Retinal complications (retinal detachment, macular edema), due to open eye surgery, are rare but may occur.

Recurrence of keratoconus: Lastly, a recurrence of keratoconus may be encountered. The mechanism of progressive myopia observed after a graft for keratoconus is not understood. Ruhswurm, et al46 observed an average myopia of –0.86 D after ablation of the sutures and a myopia of –2.35 D 3 years after the operation. This progressive myopia could be due to a recurrence of keratoconus at the level

of the grafted cornea. Published cases of recurrences of keratoconus have increased in number. 147

Keratoconus Surgery and Cross-linking

Pramanik, et al28 reported on 112 eyes of 84 patients operated with PK for keratoconus with an average follow-up of 13.8 years (range from 0.5 to 30.4 years). A recurrence of keratoconus was confirmed in 6 cases (5.4%) after an average period of 17.9 years (range of 11 to 27 years). The probability of having a recurrence of keratoconus after PK over 25 years was estimated at 11.7%.

It has not yet been clearly established whether a keratoconus recurs or a mild keratoconus from the donor that has gone unnoticed becomes manifest. However, the average time of 17 years until the onset of a recurrence of keratoconus is quite comparable with the time to natural development of keratoconus in a teenager.

Discussion/Conclusions

Will the number of indications of corneal graft for keratoconus be reduced? Would the advances in contact lenses, suppressive (corneal collagen cross-linking with Riboflavin: CXL) and additive (intracorneal rings) treatments be able to avoid or delay a corneal graft?

CXL is aimed at progressive keratoconus.47 Its purpose is to “rigidify” a cornea which is biomechanically unstable. This effect that was observed in vitro48, 49 is more difficult to quantify in vivo. However, the first clinical results are encouraging, and the efficacy will continue to be assessed over a longer period.

Of course, contact lenses, which are essentially rigid, remain the basic treatment for eyes with keratoconus. Unfortunately, lenses are not tolerated in some patients who are often those with allergies and whose corneas remain transparent. In these cases, the implantation of intracorneal rings is a worthwhile alternative treatment to a corneal graft.53, 54 A longer period of time is also necessary to assess what will become of these corneas. A combination of these two treatments (CXL/rings) or even of these three treatments (CXL/lenses/rings) may also be used.

When the progression of keratoconus leads to central corneal scarring or major thinning, a corneal graft is required. In this case, will the proportion of PK be reduced in favor of lamellar grafts?

The growing number of publications of lamellar graft techniques already marks this trend. Several studies comparing the results of PK and lamellar grafts in keratoconus have shown identical visual results.55-57 The operating technique in lamellar grafts is more difficult than that of PK but they offer notable advantages in terms of conservation of the endothelium, graft rejection, faster corneal wound healing, and a shorter duration of the use of corticosteroids.

In certain cases, when the endothelium is involved, PK remains the only surgical alternative. If not, the choice between PK and lamellar grafts depends essentially on the preference and experience of the surgeon.

Long considered as the reference surgical treatment for keratoconus, today, PK is part of a therapeutic arsenal that has been considerably enriched in the past few years. PK in keratoconus requires a perfect surgical technique. The benefits of the femtosecond laser in the surgical technique remains to be demonstrated, and the technique may still benefit from future improvements. The visual results of PK in keratoconus are good in the majority of cases. This surgery, carried out most often in young patients, may lead to complications which should be early detected, in order to detect them early and provide appropriate solutions. Thus, the surgical indication of PK in a patient with keratoconus must always take into account this benefits/risks ratio. Although PK may be increasingly replaced with lamellar grafts, nevertheless, PK is an established surgical technique in

148 keratoconus that has been greatly studied for its efficacy.